Analyses of dermal innate lymphoid cells in mice lacking T-bet and STAT6
Analyses of dermal innate lymphoid cells in mice lacking T-bet and STAT6
复制标题
缺乏 T-bet 和 STAT6 的小鼠真皮先天淋巴细胞分析
DOI：
10.1016/j.alit.2018.05.004
复制
发表时间：
2018
影响因子：
6.8
通讯作者：
Nakajima H.
中科院分区：
文献类型：
--
作者：
Makita S;Takatori H;Tamachi T;Suto A;Suzuki K;Nakajima H.
先天淋巴细胞 (ILC) 是免疫细胞的新亚群，缺乏抗原特异性受体和细胞谱系标记。 1 e3 ILC 是组织驻留细胞，不仅存在于淋巴组织和皮肤中，还存在于肺和肠道的粘膜表面。 2 ILC 通过预防感染和促进组织修复以维持组织稳态来保护前线的上皮屏障。 2、3 ILC 包括 1 型 ILC（ILC1s）、2 型 ILC（ILC2s）和 3 型 ILC（ILC3s），根据表面分子、转录因子和细胞因子的表达模式进行分类，类似于 Th1 细胞、Th2 细胞和 Th17 细胞等辅助 T 细胞。 1 e3 ILC1 表达 T-bet，并响应 IL-12、IL-15 和 IL-18 产生 IFN-g。 1, 3 ILC3 表达 RORgt，并通过响应 IL-1b 和 IL-23 产生 IL-17A 和 IL-22 来参与针对细胞外细菌的免疫应答。 1, 3 另一方面，ILC2 表达 GATA3，并响应 IL-33 和 IL-25 产生 Th2 细胞因子，例如 IL-5、IL-9 和 IL-13。 1, 3, 4 很明显，ILC2 是抗蠕虫反应所必需的，但 ILC2 的过度激活会导致过敏性炎症的发生。 3, 4 关于体内 ILC2 激活的调节机制，我们最近报道 T-bet 抑制肺 ILC2 产生 IL-9，从而抑制 IL-33 诱导的嗜酸性粒细胞气道炎症。 4 关于 ILC2 与特应性皮炎之间的关系，Salimi 等人。据报道，与健康对照相比，特应性皮炎患者皮肤中 ILC2 的数量有所增加。 5 此外，ILC2 已被证明对于 MC903（维生素 D3 类似物；卡泊三醇）诱导的小鼠特应性皮炎样皮肤炎症的发生至关重要。 5 此外，皮肤中过度表达 IL-33 的转基因小鼠已被证明会随着 ILC2 的激活而自发出现特应性皮炎样皮肤病。 6 然而，人们对 ILC 在皮肤中的积累是如何调节的以及 ILC 是否参与嗜酸性粒细胞皮肤炎症的发展知之甚少。在这方面，我们最近发现 T-bet 和 STAT6 双缺陷 (T-bet Ā/Ā STAT6 Ā/Ā) 小鼠自发地出现特应性皮炎样皮肤病（Makita 等人提交）。皮肤病在 8 周龄时开始明显，几乎所有 T-bet Ā/Ā STAT6 Ā/Ā 小鼠在 12 周龄时都出现皮肤病。在 T-bet Ā/Ā STAT6 Ā/Ā 小鼠中，皮肤中嗜酸性粒细胞、肥大细胞和 CD4 + T 细胞的数量增加，并且抗 CD4 抗体对 CD4 + T 细胞的消耗减少了
Innate lymphoid cells (ILCs) are novel subsets of immune cells which lack antigen-specific receptors and cell-lineage markers. 1 e3 ILCs are tissue-resident cells, which are found not only in lymphoid tissues and skin, but also at the mucosal surface of lung and gut. 2 ILCs protect epithelial barriers in the front line by preventing infection and by promoting tissue repair to maintain tissue homeostasis. 2, 3 ILCs consist of type 1 ILCs (ILC1s), type 2 ILCs (ILC2s), and type 3 ILCs (ILC3s), which are classified based on the expression pattern of surface molecules, transcription factors, and cytokines, analogous to helper T cells like Th1 cells, Th2 cells, and Th17 cells. 1 e3 ILC1s express T-bet, and produce IFN-g in response to IL-12, IL-15, and IL-18. 1, 3 ILC3s express RORgt, and are involved in immune responses against extracellular bacteria by producing IL-17A and IL-22 in response to IL-1b and IL-23. 1, 3 On the other hand, ILC2s express GATA3, and produce Th2 cytokines such as IL-5, IL-9, and IL-13 in response to IL-33 and IL-25. 1, 3, 4 It became clear that ILC2s are required for anti-helminth responses but the excessive activation of ILC2s results in the development of allergic inflammation. 3, 4 With respect to the regulatory mechanism of ILC2 activation in vivo, we have recently reported that T-bet suppresses IL-9 production from lung ILC2s and thereby inhibits IL-33-induced eosinophilic airway inflammation. 4 Regarding the relationship between ILC2s and atopic dermatitis, Salimi et al. have reported that the number of ILC2s is increased in the skin of patients with atopic dermatitis as compared with that of healthy controls. 5 In addition, ILC2s have been shown to be critical for the development of MC903 (vitamin D3 analog; calcipotriol)-induced atopic dermatitis-like skin inflammation in mice. 5 Furthermore, transgenic mice overexpressing IL-33 in the skin have been shown to spontaneously develop an atopic dermatitis-like skin disease, along with the activation of ILC2s. 6 However, it is poorly understood how the accumulation of ILCs in the skin is regulated and whether ILCs are involved in the development of eosinophilc skin inflammation.In this regard, we have recently found that T-bet-and STAT6-double-deficient (T-bet Ā/Ā STAT6 Ā/Ā) mice spontaneously develop an atopic dermatitis-like skin disease (Makita et al., submitted). The skin disease started being apparent at 8-week-old and almost all T-bet Ā/Ā STAT6 Ā/Ā mice developed the skin disease by 12-week-old. In T-bet Ā/Ā STAT6 Ā/Ā mice, the numbers of eosinophils, mast cells, and CD4 þ T cells in the skin are increased, and the depletion of CD4 þ T cells by anti-CD4 antibody decreases the number of